The extrathoracic airways influence breathing a great deal, but their physiology has been neglected until fairly recently. The purpose of this project has been to explore and define the influence of the upper airways on the control of breathing. Both sensory and motor mechanisms have been examined, and substantial progress has been made. This application seeks continuing support for this project, to enable us to study three major problems: (1) the inhibition of breathing by physiologically relevant concentrations of CO2 in the laryngeal airway, (2) the modulating influence of vagal afferents on respiratory reflexes from the larynx and elsewhere, and (3) the complex interactions of pressure, flow, resistance, muscle activities and airway calibre in the pharyngeal and nasal segments of the respiratory tract. The proposed studies are based on observations made during the current funding period. We believe these studies will advance substantially the understanding of upper airway physiology and thus ultimately contribute to improving the diagnosis and management of clinical disorders of the respiratory system.